Strategies in new drug discovery often look to natural products for leads in finding new chemical compounds with therapeutic properties. One of the recurring problems in drug discovery is the availability of organic compounds derived from natural sources. Techniques employing combinatorial chemistry attempt to overcome this problem by allowing the high throughput synthesis and testing of hundreds or thousands of related synthetic compounds, called a chemical library. In designing the synthesis of a prospective therapeutic compound or a chemical library, one often looks to natural chemical motifs which are known to have broad biological activity.
Pyrazole has a long history of application in pharmaceutical and agrochemical industry, and posses a widespread occurrence as sub-structures in a large variety of compounds, which exhibit important biological activities and pharmacological properties. Elguero, J. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.; Pergamon-Elsevier Science: Oxiford, 1996; Vol. 6, pp. 1-75; (b) Sutharchanadevi, M.; Murugan, R. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.; Pergamon-Elsevier Science: Oxiford, 1996; Vol. 6, pp. 221-260.
Infection with the Hepatitis C virus (HCV) represents a serious world-wide health crisis. In more than 70% of infected individuals, the virus evades clearance by the immune system leading to a persistent HCV infection. The long term effects of persistent HCV infection range from an apparently healthy carrier state to chronic hepatitis, liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma. HCV is a leading cause of chronic liver disease. The best therapy currently available for treatment of HCV infection uses a combination of pegylated α-interferon and ribavirin. However, many of the patients treated with this therapy fail to show a sufficient antiviral response. Additionally, interferon treatment also induces severe side-effects (i.e. retinopathy, thyroiditis, acute pancreatitis, depression) that diminish the quality of life of treated patients. Thus, it is vital that more effective treatments be identified.